The general objective of the projects outlined in this grant application is to continue a research program that contributes to the knowledge of the chemistry and biological action of protein hormones. One particular objective is to extend our studies of the structure of human chorionic gonadotropin to arrive at completely confirmed estimates of the primary structure of both the alpha and beta subunits of this glycoprotein hormone. In addition, it is proposed to study the relationship of this hormone's structure to its biological action by preparing various hormone derivatives and studying their potential for biological activity or for competitive inhibition of binding of the native hormone on target cells. A second major objective of the work discussed in this application is to complete a determination of the structure of the subunits of the thyroxine binding protein, human prealbumin. These data are being obtained in a collaborative study with other workers who are determining the three-dimensional structure of this protein by X-ray crystallographic analysis. When complete, this study should provide an understanding of the interactions that lead to the high affinity for thyroxine by this protein. A third objective of the research outlined here is to continue clinical studies of the effectiveness of various forms of medical treatment of Paget's Disease of bone including calcitonin and ethane hydroxydiphosphonic acid. In addition, the effects of these two compounds will be studied in other forms of calcium disorders and metabolic bone disease.